Reconstruction and Functional Annotation of P311 Protein–Protein Interaction Network Reveals Its New Functions

Abstract

P311 is a highly conserved multifunctional protein. However, it does not belong to any established family of proteins, and its biological function has not been entirely determined. This study aims to reveal the unknown molecular and cellular function of P311. OCG (Overlapping Cluster Generator) is a clustering method used to partition a protein-protein network into overlapping clusters. Multifunctional proteins are at the intersection of relevant clusters. DAVID is an analytic tool used to extract biological meaning from a large protein list. Here we presented OD2 (OCG + DAVID + 2 human PPI datasets), a novel strategy to increase the likelihood to identify biological functions most pertinent to the multifunctional proteins. The principle of OD2 is that OCG prepares the protein lists from multifunctional protein relevant overlapping clusters, for a functional enrichment analysis by DAVID, and the similar functional enrichments, which occurs simultaneously when analyzing two human PPI datasets, are supposed to be the predicted functions. By applying OD2 to two reconstructed human PPI datasets, we supposed the function of the P311 in inflammatory responses, cell proliferation and coagulation, which were confirmed by the following biological experiments. Collectively, our study preliminarily found that P311 could play a role in inflammatory responses, cell proliferation and coagulation. Further studies are required to validate and elucidate the underlying mechanism.

Structural variants in the Epb41l4a locus: TAD disruption and Nrep gene misregulation as hypothetical drivers of neurodevelopmental outcomes

“…This protein is highly conserved across species and is typically expressed in the nervous system 15 as well as in vascular and visceral smooth muscle beds 16 , 17 . Despite not belonging to any recognized protein family or having signature motifs indicating function, it contains three PEST-like domains, which are subject to rapid degradation via the ubiquitin–proteasome system 18 – 20 . NREP is known to enhance cell proliferation 19 and migration 16 during vascularization and wound healing 21 – 24 and is involved in the development of various cancer types 25 – 28 .…”